Advanced Search
Submit one or more of the following items, and they will be searched along with your query in the search box above.
Any submit button will submit all of the items you have changed.

+ Publication-Date Published in the last:

30 days
60 days
90 days
6 months
12 months
this year
2 years
3 years
5 years
10 years

Or published in the following date range:
From (yyyy/mm/dd - month and day are optional) to ('to' is optional)
+ Full Text
Retrieve articles with hyperlinks to:
full text (either free or subscription)
free full text
subscription full text
no full text link
+ Sort-Order
Sort the retrieved articles by:
relevance
publication date
+ Language And with languages:

+ Species
And for:
Humans
Animals
+ Gender
And for:
Male
Female
+ Age And for these age groups:

Newborn: birth to 1 month
Infant: 1 to 23 months
Preschool child: 2 to 5 years
Child: 6 to 12 years
Adolescent: 13 to 18 years
Adult: 19 to 44 years
Middle aged: 45 to 64 years
Aged: 65+ years
80 and over: 80+ years

+ Title
And for this query matching the titles:
+ Transliterated-Title
And for this query matching the title in original language:
+ Abstract
And for this query matching the abstratcs:
+ Major-Mesh
And for this query matching the MeSH-Major terms:
+ Mesh
And for this query matching any MeSH terms:
+ Journal
And for one or more of these journal abbreviated names:
OR OR
(see title abbreviations)+ Volume
And with journal volume number:
+ Issue
And with journal issue number:
+ Page
And with page number:
+ ISSN
And with ISSN:
+ Publication-Place
And with journal's country of publication:
+ Author

+ Affiliation
And with affiliation to:
+ Has-Abstract
Find MEDLINE records with the abstract status:
has abstract
does not have abstract
include both record types
include both record types but rank higher the records having abstract (the default BML behavior) + PMID
Show me only articles for these PMIDs (PubMed IDs):

Page Format
Any submit button will submit all of the items you have changed.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most fulminant human malignancies.

From the extended list, they focused on hypothetical and anonymous genes and investigated a novel gene, named the overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) gene.

METHODS: To investigate the role of the OEATC-1 gene in ATC carcinogenesis, first, the expression levels of OEATC-1 in ACLs, in various types of carcinoma cell lines, and in normal human tissues were examined with reverse transcriptase-polymerase chain reaction analysis.

To explore the effect of OEATC-1 in ATC development, a cell-growth assay was performed with KTA2 cells under OEATC-1 gene silencing using small-interfering RNA (siRNA).

RESULTS: OEATC-1 was overexpressed significantly in ACLs and in other types of carcinoma cell lines with various expression levels.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] FOXA1 is a potential oncogene in anaplastic thyroid carcinoma.

Here, we investigated the potential role of FOXA1 in human thyroid carcinomas.

EXPERIMENTAL DESIGN: We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors.

In addition, we examined the role of FOXA1 in the proliferation of an undifferentiatedthyroid carcinoma cell line by short hairpin RNA-mediated silencing.

RESULTS: We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC).

In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases.

Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation.

Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing.

CONCLUSIONS: FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line.

Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Poorly differentiated and anaplastic thyroid cancer.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC) comprise a small subset of thyroid tumors that are associated with a poor prognosis and account for a significant portion of the morbidity and mortality related to thyroid cancer.

PDTC may represent an intermediate entity in the progression of well-differentiated thyroid carcinoma to ATC.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: The epidermal growth factor receptor (EGFR) has been reported to be overexpressed in anaplastic thyroid carcinoma (ATC).

In vitro studies have shown that EGFR tyrosine kinase inhibitors (TKIs) greatly inhibit cellular growth and induced apoptosis in the ATC cell lines, while somatic mutations in the tyrosine kinase domain or an increased gene copy number are associated with increased sensitivity to TKIs in non-small cell lung cancer.

High polysomy was observed in all 10 cases with giant cell subtype, but in only 4/11 (36.3%) with squamoid and 0/2 with spindle cell sarcomatoid subtype.

CONCLUSION: Despite the low incidence of somatic EGFR gene mutation and amplification in the study samples, in view of the fact that high polysomy was often identified by FISH, as well as the current lack of therapeutic options, EGFR TKIs are worth investigating for treating the patients with ATC who have at least giant cell subtype.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: Integrin α6β4 is a known tumor antigen; however, its function in different subtypes of thyroid cancer is not known.

This study reports that α6β4 expression is selectively up-regulated in anaplastic thyroid cancer (ATC) cells, the most malignant subtype of human thyroid cancer.

MATERIALS AND METHODS: To assess the contribution of α6β4 in ATC progression, cell proliferation, motility and soft agar assay were performed in vitro and a xenograft tumor growth assay was performed in vivo.

CONCLUSION: These data suggest that integrin α6β4 contributes to the development of aggressive forms of thyroid cancer with poor prognostic potential, such as ATC, and thus may be a novel therapeutic target for the treatment for this subtype of thyroid cancer.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Micro RNAs (miRNAs) are non-coding small RNAs and constitute a novel class of negative gene regulators that are found in both plants and animals.

Several miRNAs play crucial roles in cancer cell growth.

To identify miRNAs specifically deregulated in anaplastic thyroid cancer (ATC) cells, we performed a comprehensive analysis of miRNA expressions in ARO cells and primary thyrocytes using miRNA microarrays.

On the other hand, miR-18a inhibitor only moderately attenuated the cell growth.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than 1 year after diagnosis.

During the course of a program to screen a panel of ATC cell lines for genomic copy-number aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11.22 and belongs to the homologous to the E6-associated protein carboxylterminus ubiquitin ligase family.

The expression of ITCH was increased in 4 of 14 ATC cell lines (28.6%), including 8305C in which there was a copy-number amplification of this gene, and six of seven primary cases (85.7%).

Among the primary thyroid tumors, a considerable number of ITCH high expressers was found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%).

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Anaplastic thyroid carcinoma (ATC) is among the most aggressive malignancies known and is characterized with rapid growth, early invasion, and complete refractoriness to current therapies.

Here we report that triptolide, a small molecule from a Chinese herb, could potently inhibit proliferation in vitro, angiogenesis in vivo, and invasion in a Matrigel model in human ATC cell line TA-K cells at nanomolar concentrations.

Expression of the NF-kappaB targeting genes cyclin D1, vascular endothelial growth factor, and urokinase-type plasminogen activator is significantly reduced by triptolide in both TA-K and 8505C human ATC cell lines, which are well known to be critical for proliferation, angiogenesis, and invasion in solid tumors.

Our findings suggest that triptolide may function as a small molecule inhibitor of tumor angiogenesis and invasion and may provide novel mechanistic insights into the potential therapy for human ATC.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

CONTEXT: Anaplastic thyroid carcinomas (ATC) are among the most aggressive human malignancies and are characterized by high mitotic activity.

OBJECTIVE: In an attempt to cast light on the mechanisms governing ATC, we evaluated MCM5 and MCM7 expression in human normal, papillary (PTC), and anaplastic thyroid samples, as well as in primary culture cells and transgenic mouse models.

RESULTS: MCM5 and MCM7 expression was high in 65% of ATC and negligible in normal thyroid tissue and papillary thyroid carcinomas.

An analysis of human ATC primary cell cultures and of a transgenic mouse model of ATC confirmed these findings.

An increased transcription rate accounted for MCM7 up-regulation, because the activity of the MCM7 promoter was more than 10-fold higher in ATC cells compared with normal thyroid cells.

Treatment with small inhibitory duplex RNAs, which decrease MCM7 protein levels, reduced the rate of DNA synthesis in ATC cells.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: Anaplastic thyroid cancer is an endocrine malignancy.

Little is known regarding the expression by anaplastic tumors of molecular targets for new human anticancer agents that have been studied in the preclinical or clinical setting.

The objective of this work was to evaluate the expression profile of anaplastic thyroid tumors for molecular targets for treatment.

METHODS: Of the 94 cases of anaplastic thyroid cancers diagnosed and treated in British Columbia, Canada over a 20-year period (1984-2004), 32 cases (34%) had adequate archival tissue available for evaluation.

A tissue microarray was constructed from these anaplastic thyroid tumors and immunohistochemistry was utilized to evaluate expression of 31 molecular markers.

RESULTS: A single tumor with strong calcitonin expression was identified as a poorly differentiated medullary carcinoma and excluded from the study cohort.

The mean age of the anaplastic cohort was 66 years; 16 patients (51%) were females, and the median patient survival was 23 weeks.

A wide range in molecular marker expression was observed by the anaplastic thyroid cancer tumors (0-100%).

CONCLUSIONS: Anaplastic thyroid tumors exhibit considerable derangement of their cell cycle and multiple signal transduction pathways that leads to uncontrolled cellular proliferation and the development of genomic instability.

This report is the first to comprehensively evaluate a panel of molecular targets for therapy of anaplastic thyroid cancer and supports the development of clinical trials with agents such as cetuximab, small-molecule tyrosine kinase inhibitors, and aurora kinase inhibitors, which may offer new hope for individuals diagnosed with this fatal thyroid malignancy.

Anaplastic carcinoma of the thyroidgland (ACT) is a highly malignant tumor that is almost invariably associated with a fatal outcome.

The spindle cell variant of ACT is usually indistinguishable from a true sarcoma and it can simulate fibrosarcoma, malignant fibrous histiocytoma (MFH), hemangiopericytoma and angiosarcoma or rhabdomyosarcoma.

Both cases disclosed a very similar histological appearance, with a main population of small, pleomorphic, round-to-oval cells arranged in a storiform pattern, admixed with scattered pleomorphic giant cells, an image similar to that of the usual type of MFH.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Despite advances in the management of thyroid carcinoma and other solid tumors, metastasis continues to be the most significant cause in cancer mortality.

OBJECTIVE: Our objective was to examine the effects of S100A4 expression knockdown by RNA interference on the growth and metastasis of human anaplastic thyroid carcinoma cells (ARO) and the sensibility of ARO to paclitaxel after S100A4 knockdown.

DESIGN: A plasmid construct was made that expressed small hairpin RNA (shRNA) specific for S100A4.

The growth rate of ARO/S100A4-shRNA was reduced by 46 +/- 7.6% in a cell proliferation assay.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Anaplastic thyroid cancer (ATC) is one of the most lethal of all human tumors, but cytogenetic information concerning ATC is extremely limited.

Using our in-house array-based comparative genomic hybridization and 14 ATC cell lines with further fluorescence in situ hybridization analysis, we demonstrated amplification of the DUSP26 gene, known by another report as MAP kinase phosphatase-8.

To establish whether ATC could be a target of PPAR gamma agonists, we first examined PPAR gamma protein expression in a panel of six ATC cell lines and then studied the biologic effects of two PPAR gamma agonists, ciglitazone and rosiglitazone, that belong to the class of thiazolidonediones.

PPAR gamma protein was present and functional in all ATC cell lines.

Rosiglitazone-induced growth inhibition was associated with cell cycle arrest and changes in cell cycle regulators, such as an increase of cyclin-dependent kinases inhibitors p21(cip1) and p27(kip1), a decrease of cyclin D1, and inactivation of Rb protein.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Phorbol 12-myristate 13-acetate (PMA) is known to affect a variety of cellular processes, including cell proliferation, differentiation, and migration.

Our findings show that PMA induced a strong antiproliferative effect in two anaplastic (FRO and ARO) and one follicular (ML-1) thyroid cancer cell lines, and increased the fraction of FRO cells in G1 phase of the cell cycle.

Moreover, PMA evoked a significant increase in the levels of the cell cycle regulators p21Waf1/Cip1 and p27Kip1.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

B-Raf is an important mediator of cell proliferation and survival signals transduced via the Ras-Raf-MEK-ERK cascade.

BRAF mutations have been detected in several tumors, including papillary thyroid carcinoma, but the precise role of B-Raf as a therapeutic target for thyroid carcinoma is still under investigation.

We analyzed a panel of 93 specimens and 14 thyroid carcinoma cell lines for the presence of BRAF mutations and activation of the mitogen-activated protein/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway.

We also compared the effect of a B-Raf small inhibitory RNA construct and the B-Raf kinase inhibitor AAL881 on both B-Raf wild-type and mutant thyroid carcinoma cell lines.

We found a high prevalence of the T1799A (V600E) mutation in papillary and anaplastic carcinoma specimens and cell lines.

Immunodetection of phosphorylated and total forms of MEK and ERK revealed no difference in their phosphorylation between wild-type and BRAF(V600E) patient specimens or cell lines.

Furthermore, a small inhibitory RNA construct targeting the expression of both wild-type B-Raf and B-Raf(V600E) induced a comparable reduction of viability in both wild-type and BRAF(V600E) mutant cancer cells.

We conclude that B-Raf is important for the pathophysiology of thyroid carcinomas irrespective of mutational status.

Small molecule inhibitors that selectively target B-Raf(V600E) may provide clinical benefit for patients with thyroid cancer.

BACKGROUND: B-Raf(V600E) is a frequent mutation in anaplastic thyroid cancers and is a novel therapeutic target.

Three out of 6 mice receiving PLX4720+thyroidectomy had no evidence of tumor at 35 days; the other 3 mice had small tumors (average 1.4 mm(3)) and showed no signs of metastatic disease.

CONCLUSION: Thyroidectomy with neoadjuvant PLX4720 could be an effective therapeutic strategy for early anaplastic thyroid cancers that harbor the B-Raf(V600E) mutation and are refractory to conventional therapeutic modalities.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] BRAF is a therapeutic target in aggressive thyroid carcinoma.

PURPOSE: Oncogenic conversion of BRAF occurs in approximately 44% of papillary thyroid carcinomas and 24% of anaplastic thyroid carcinomas.

In papillary thyroid carcinomas, this mutation is associated with an unfavorable clinicopathologic outcome.

Our aim was to exploit BRAF as a potential therapeutic target for thyroid carcinoma.

EXPERIMENTAL DESIGN: We used RNA interference to evaluate the effect of BRAF knockdown in the human anaplastic thyroid carcinoma cell lines FRO and ARO carrying the BRAF V600E (V600EBRAF) mutation.

We also exploited the effect of BAY 43-9006 [N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoyl pyridin-4-yl)oxyphenyl)urea], a multikinase inhibitor able to inhibit RAF family kinases in a panel of six (V600E)BRAF-positive thyroid carcinoma cell lines and in nude mice bearing ARO cell xenografts.

RESULTS: Knockdown of BRAF by small inhibitory duplex RNA, but not control small inhibitory duplex RNA, inhibited the mitogen-activated protein kinase signaling cascade and the growth of ARO and FRO cells (P < 0.0001).

Although BRAF knockdown led to apoptosis in the melanoma cell line A375, the anaplastic thyroid carcinoma cell ARO underwent growth arrest upon silencing, with little or no cell death.

The different outcome of BRAF down-regulation in the two cell lines was associated with an opposite regulation of p21(CIP1/WAF1) expression levels in response to the block of the BRAF mitogenic signal.

These results were confirmed using a specific BRAF small-molecule inhibitor, PLX4032.

Altogether, our data indicate that oncogenic BRAF inhibition can have a different effect on cell fate depending on the cellular type.

Furthermore, we suggest that a BRAF-independent mechanism of cell survival exists in anaplastic thyroid cancer cells.

Use of this combination treatment of Gefitinib and ionizing radiation may be a promising therapy for anaplastic thyroid and metastatic follicular thyroid cancer and should be extended into animal models.

Micro-RNAs (miRNAs) belong to a class of small non-coding messenger RNA species that have emerged as potent regulators of a variety of biological processes including oncogenesis.

Currently, a considerable degree of interobserver variability exists in the morphological diagnosis of certain types of thyroid carcinomas especially the follicular pattern neoplasm.

The prediction of progression of these differentiated carcinoma to more aggressive forms like poorly differentiated and anaplastic types is of considerable interest to physicians and pathologists for determining prognosis and making therapeutic decisions.

Several investigators have proposed a more cohesive approach to thyroid cancer diagnosis incorporating molecular and proteomics based tools in addition to the conventional morphological diagnosis.

In this context, miRNAs serve as an important diagnostic tool, and several studies have demonstrated their utility as class identifiers especially in the context of follicular thyroid carcinoma, papillary thyroid carcinoma and anaplastic thyroid carcinoma.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] New molecular targeted therapies in thyroid cancer.

Carcinoma of the thyroidgland is the most common malignancy of the endocrine system.

A small percentage of such patients, however, do not undergo remission and need new therapeutic approaches.

Both anaplastic and medullary thyroid carcinomas exhibit aggressive behavior and are usually resistant to current therapeutic modalities.

Thyroid carcinoma represents a fascinating model and a particularly promising paradigm for targeted therapy because some of the key oncogenic events are activating mutations of genes coding for tyrosine kinases, and these occur early in cancer development.

Mutations in the RET proto-oncogene have been identified as causative for papillary carcinoma and familial medullary thyroid carcinoma, making it an attractive target for selective inhibition in these subtypes.

ZD 6474 has shown promising activity in preclinical models against RET kinase, and its contemporary inhibition of vascular endothelial growth factor and epidermal growth factor pathways renders it a very attractive drug for clinical trials in thyroid cancer.

Activating point mutation of B-RAF can occur early in the development of papillary carcinoma.

Clinical evaluation of B-RAF-targeting drugs is undergoing and trials in thyroid cancer are planned.

Agents that restore radioiodine uptake, such as histone deacetylase inhibitors and retinoids, represent another exciting field in new drug development in thyroid cancer.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] IQGAP1 plays an important role in the invasiveness of thyroid cancer.

PURPOSE: This study was designed to explore the role of IQGAP1 in the invasiveness of thyroid cancer and its potential as a novel prognostic marker and therapeutic target in this cancer.

EXPERIMENTAL DESIGN: We examined IQGAP1 copy gain and its relationship with clinicopathologic outcomes of thyroid cancer and investigated its role in cell invasion and molecules involved in the process.

We also report here that TRAIL-induced thyroid cancer cell apoptosis is mediated by oxidative stress and that DJ-1, a potent nutritional antioxidant, protects cancer cells from apoptosis at least in part by impeding the elevation of reactive oxygen species levels induced by TRAIL and impairing caspase-8 activation.

The protein was not detectable in the 52 specimens of normal thyroid, while 70 out of 74 analyzed carcinomas (33 out of 33 follicular, 17 out of 19 papillary, 12 out of 13 medullar, and 8 out of 9 anaplastic) were clearly positive for DJ-1 expression.

Our data demonstrated that DJ-1 is specifically expressed in thyroid carcinomas and not in the normal thyroid tissue.

In addition, the protein modulates the response to TRAIL-mediated apoptosis in human neoplastic thyroid cells, at least partially through its antioxidant property.

We report such a tumor involving the bilateral lobes of the thyroid which showed simultaneous chondrosarcomatous, osteosarcomatous, fibrosarcomatous and rhabdomyosarcomatous differentiation.

Microscopically, the tumor was composed of small primitive mesenchymal cells with osteoid formation resembling the small cell variant of osteosarcoma interspersed with multiple cartilaginous nodules that indicated chondrosarcomatous differentiation.

Immunohistochemically, the small primitive mesenchymal cells were positive for vimentin and CD99 and negative for CD56, Syn, CgA, CK, TG, TTF-1, calcitonin, and S-100.

Primary malignant mesenchymoma of the thyroid is a high-grade malignant tumor with a poor prognosis.

Its differerential diagnosis includes anaplastic carcinoma and other rare sarcomas with chondroid, osteoid, and other mesenchymal metaplasia.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

OBJECTIVE: To investigate the regulation of the breast cancer resistance protein ABCG2/BRCP1 drug transporter by epidermal growth factor receptor (EGFR) kinase activity, and to determine whether gefitinib, an EGFR small molecule inhibitor, will modulate the effects of doxorubicin hydrochloride by inhibiting its extrusion from thyroid cancer cells.

DESIGN: Extrusion assays using flow cytometry analysis were used to determine the ability of thyroid cancer cells to extrude the chemotherapy drug, doxorubicin, via the ABCG2 drug transporter in the presence or absence of gefitinib.

The ABCG2 expression in ARO and WRO cell lines was analyzed by Western blot analysis.

Colony formation assays were performed to determine the effect of gefitinib on thyroid cancer cell survival in response to gefitinib, doxorubicin, or the combination of both drugs.

RESULTS: Inhibition of EGFR kinase activity by gefitinib causes the translocation of the ABCG2 drug transporter away from the plasma membrane, resulting in a concomitant decrease in doxorubicin extrusion in thyroid cancer cell lines.

The addition of gefitinib increases doxorubicin-induced cell death in thyroid cancer cells as measured by colony formation assay.

Inactivation of the EGFR kinase by gefitinib potentiates the cytotoxic effect of doxorubicin in thyroid cancer, most likely by decreasing the ability of the cell to extrude doxorubicin.

The expression of ABCG2 may explain in part the ineffectiveness of doxorubicin as a single modality treatment for anaplastic thyroid cancer or for treatment of metastatic follicular thyroid cancer.

Use of this combination treatment of gefitinib and doxorubicin may be a promising therapy for anaplastic thyroid and metastatic follicular thyroid cancer and needs to be investigated further.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

OBJECTIVE: The objective of this study was to analyze BAG3 expression in thyroid neoplastic cells and investigate its influence in cell apoptotic response to TNF-related apoptosis-inducing ligand (TRAIL).

DESIGN, SETTING, AND PATIENTS: We investigated BAG3 expression in human thyroid carcinoma cell lines, including NPA, and the effect of BAG3-specific small interfering RNA on TRAIL-induced apoptosis in NPA cells.

MAIN OUTCOME MEASURES: The main outcome measures were: analysis of BAG3 protein in NPA cells by Western blot and immunocytochemistry; analysis of apoptosis in TRAIL-stimulated NPA cells by flow cytometry; and evaluation of BAG3 expression in specimens from thyroid lesions by immunohistochemistry.

The protein was not detectable in 19 of 20 specimens of normal thyroid or goiters, whereas 54 of 56 analyzed carcinomas (15 follicular, 28 papillary, and 13 anaplastic) were clearly positive for BAG3 expression.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title]Thyroid cancer: emerging role for targeted therapies.

The histology and clinical behavior of thyroid cancer are highly diverse.

Although most are indolent tumors with a very favorable outcome with the current standard of care therapy, a small subset of tumors may be among the most lethal malignancies known to man.

While surgery and radioactive iodine are the standard of care for differentiated thyroid cancers (DTC) and are effective in curing a majority of such patients, those with iodine-resistant cancers pose a great challenge for clinicians, as these patients have limited treatment options and poor prognoses.

Medullary thyroid carcinoma (MTC) has no effective systemic therapy despite the genetic and signaling defects that have been well characterized for the last two decades.

Anaplastic thyroid cancer (ATC) is one of the most aggressive solid tumors that remains fatal despite conventional multimodality therapy.

Increased understanding of the pathogenesis of papillary thyroid carcinoma, the most common type of DTC, as well as ATC, has led to the development of targeted therapies aimed at signaling pathways and angiogenesis that are critical to the development and/or progression of such tumors.

Conduction of such trials in the last few years represents a major breakthrough in the field of thyroid cancer.

Several trials testing targeted therapies offer promise for setting new standards for the future of patients with progressive thyroid cancer.

The purpose of this paper is to outline the recent advances in understanding of the pathogenesis of thyroid cancer and to summarize the results of the clinical trials with these targeted therapies.

[Email]Email this result itemEmail the results to the following email address: [X] Close

In this study, we tested the hypothesis that BRAF(V600E) mutation influences hypoxia-inducible factor-1alpha expression in papillary thyroid carcinoma cells.

A BRAF wild-type papillary thyroid carcinoma cell line and a BRAF(V600E) mutated papillary thyroid carcinoma cell line were selected to study the effects of BRAF mutation on hypoxia-inducible factor-1alpha expression in vitro.

[Title] RbAp48 is a target of nuclear factor-kappaB activity in thyroid cancer.

The inhibition of NF-kappaB in the anaplastic thyroid carcinoma cell line (FRO) leads to increased susceptibility to apoptosis induced by chemotherapeutic drugs and to the block of oncogenic activity.

OBJECTIVES: To understand better the molecular mechanisms played by NF-kappaB in thyroid oncogenesis, we performed a differential proteomic analysis between FRO transfected with a superrepressor form of inhibitor of kappaBalpha (IkappaBalphaM) and the parental counterpart (FRO Neo cells).

Reduction of RbAp48 expression using small interfering RNA determined the suppression of tumorigenicity, very likely due to the decrease of their growth rate rather than to an increased susceptibility to apoptosis.

CONCLUSION: Our results show that RbAp48 is a NF-kappaB-regulated gene playing an important role in thyroid cancer cell autonomous proliferation.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Reactive oxygen species, specifically hydrogen peroxide (H(2)O(2)), have a significant role in hormone production in thyroid tissue.

Although recent studies have demonstrated that dual oxidases are responsible for the H(2)O(2) synthesis needed in thyroid hormone production, our data suggest a pivotal role for superoxide dismutase 3 (SOD3) as a major H(2)O(2)-producing enzyme.

According to our results, Sod3 is highly expressed in normal thyroid, and becomes even more abundant in rat goiter models.

We showed TSH-stimulated expression of Sod3 via phospholipase C-Ca(2+) and cAMP-protein kinase A, a pathway that might be disrupted in thyroid cancer.

In line with this finding, we demonstrated an oncogene-dependent decrease in Sod3 mRNA expression synthesis in thyroid cancer cell models that corresponded to a similar decrease in clinical patient samples, suggesting that SOD3 could be used as a differentiation marker in thyroid cancer.

Finally, the functional analysis in thyroid models indicated a moderate role for SOD3 in regulating normal thyroid cell proliferation being in line with our previous observations.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: The aim of this present study is to define the significance of recurrent laryngeal nerve palsy (RLNP) detected before surgery for thyroid diseases with regard to the incidence of malignancy, histopathologic distribution, extrathyroidal invasion, management, and prognosis.

METHODS: Six hundred and twenty-two patients underwent operation for various thyroid disease and were treated by the same surgeon.

The study was confined to 16 (3%) patients who suffered from a thyroid tumor with preoperative RLNP.

RESULTS: Of these 16 patients, 1 had benign thyroid disease, while the other 15 had malignancy (94%).

The recurrent laryngeal nerve could be dissected from the thyroid neoplasm in 3 patients, 2 of whom experienced recovery of this nerve's function postoperatively.

Similarly, pharmacological inhibition of the phosphoinositide 3-kinase (PI3K) pathway using LY294002 inhibited HIF-1 alpha and HIF-1 alpha targets in all cell lines, including those with B-RAF mutations (BcPAP and 8505c).

HIF-1 is functionally expressed in thyroid carcinomas and is regulated not only by hypoxia but also via growth factor signalling pathways and, in particular, the PI3K pathway.

Given the strong association of HIF-1 alpha with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas.

There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer.

Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation.

Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China.

IN CONCLUSION: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

NF-kappaB is constitutively activated in primary human thyroid tumors, particularly in those of anaplastic type.

The inhibition of NF-kappaB activity in the human anaplastic thyroid carcinoma cell line, FRO, leads to an increased susceptibility to chemotherapeutic drug-induced apoptosis and to the blockage of their ability to form tumors in nude mice.

To identify NF-kappaB target genes involved in thyroid cancer, we analyzed the secretome of conditioned media from parental and NF-kappaB-null FRO cells.

NGAL is highly expressed in human thyroid carcinomas, and knocking down its expression blocks the ability of FRO cells to grow in soft agar and form tumors in nude mice.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Benign nodular goiter with spindle cell component.

The spindle cells were bland, and showed short fascicular pattern or formed small nests.

Immunohistochemically, they were positive for thyroglobulin and thyroid transcription factor-1.

We thought that the spindle cells are derived from follicular cell and non-neoplastic, and it is important to recognize this lesion to distinguish from aggressive and lethal components seen in papillary carcinoma or anaplastic carcinoma.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Identification and evaluation of a new tumor cell-binding peptide, FROP-1.

Because currently known peptides are restricted to a small number of tumors, new molecules and their corresponding receptors have to be identified to enlarge the spectrum of malignancies that can be diagnosed or treated using tumor-targeting peptides.

METHODS: A 12-amino-acid peptide phage display system was applied to identify a new peptide binding to follicular thyroid carcinoma cells.

The properties of the radiolabeled peptide were assessed in binding, competition, and internalization experiments in a variety of tumor cell lines including FRO82-2 and MCF-7 cells, and the pharmacokinetic behavior of the radiolabeled peptide was evaluated in tumor-bearing mice.

It showed binding to follicular thyroid carcinoma as well as anaplastic thyroid carcinoma, mammary carcinoma, cervix carcinoma, prostate carcinoma, and cell lines derived from head and neck tumors, and low affinity could be observed to control cells such as human umbilical vein endothelial cells or immortalized keratinocytes.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Preclinical evaluation of ZD1839 alone or in combination with oxaliplatin in a panel of human tumor cell lines -- implications for clinical use.

However, in non-small cell lung cancer (NSCLC), addition of ZD1839 (Iressa) to combination chemotherapy did not improve the therapeutic outcome.

MATERIALS AND METHODS: In the present study, the activity of ZD1839 alone or in combination with oxaliplatin (Eloxatin) was evaluated in 12 human cancer cell lines including colon, testicular, anaplastic thyroid and epidermoid carcinoma cells.

RESULTS: The EGF-receptor protein was overexpressed in line A431 (epidermoid carcinoma) and near the minimum detection limit in all other cell lines.

The single agent activity of ZD1839 was highest in cell line A431.

In the other cell lines, it was lower and appeared to be independent of EGF-receptor expression levels.

Combined exposure to oxaliplatin and ZD1839 (IC30) resulted in significant synergy in 4 out of 6 colorectal cancer (CRC) cell lines and significant antagonism in 4 out of 6 non-colorectal cancer cell lines.

Continuous exposure to ZD1839 (IC30) induced a marked G1-phase arrest and dephosphorylation of EGF-receptor in A431, whereas no significant cell cycle perturbation could be detected in the low-expression cell lines.

Other factors than cell cycle perturbation seem to determine the mode of drug interaction between oxaliplatin and ZD1839.

CONCLUSION: Based on RAA, the single agent activity of ZD1839 in the investigated cell line panel appeared to be low.

Combined exposure to ZD1839 and oxaliplatin exerted synergy in colorectal cancer cell lines, warranting further evaluation in this type of cancer.

However, based on the observed antagonism in non-colorectal cancer cell lines, combined treatment with ZD1839 and oxaliplatin is not recommended for other types of cancer.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Based on histological and immunohistochemical analysis, four dogs were diagnosed with ectopic follicular cell thyroid carcinomas, one dog with ectopic medullary cell thyroid carcinoma, two dogs with neuroendocrine carcinomas and two dogs with anaplastic carcinomas.

Local invasion, pleural effusion and metastasis did not have a negative impact on survival time in this small case series.